Monoclonal antibody technology provides an important and useful tool in the study of population exposure to carcinogens. Carcinogens are known to adduct to human DNA. The presence of these carcinogen DNA adducts can be detected by monoclonal antibodies directed against specific products. Following the mouse model systems, constitutents of tobacco smoke condensate as well as metabolites of nitrosoureas adducted to DNA have been used as immunogens. Protamine has been used as a carrier in the immunization in order to avoid problems with assay techniques that involve other animal proteins. Antibodies directed against carcinogen DNA adducts have been produced in the immunized mice. Spleen cells from these mice have been fused with mouse myeloma proteins and clones of cells producing antibody against the aimmunogen have been isolated. This laboratory has also demonstrated that humans may develop antibodies to potential carcinogens to which they are exposed. It is therefore important to develop a system of production of human monoclonal antibodies. To this end, a number of established myeloma and B cell lines have been screened for the capability to be fused with human B cells. A model system has been established whereby chronic lymphocytic leukemia cells have been fused to a human myeloma cell line. The product of this cell line was the predominant cell surface immunoglobulin found on the chronic lymphocytic leukemia cells. This immunoglobulin was then used to produce a monoclonal antibody in mice and the antibody selected on the basis of restricted reactions to the specific immunoglobulin. Thus an anti-idiotype monoclonal antibody has been produced. The results demonstrate the capability of using human materials, B cells, and myeloma cell lines to produce monoclonal antibodies.